Prenatal Organophosphorus Pesticide Exposure and Child Neurodevelopment at 24 Months: An Analysis of Four Birth Cohorts

Background: Organophosphorus pesticides (OPs) are used in agriculture worldwide. Residential use was common in the United States before 2001. Objectives: We conducted a pooled analysis of four birth cohorts (children's centers; n = 936) to evaluate associations of prenatal exposure to OPs with child development at 24 months. Methods: Using general linear models, we computed site-specific and pooled estimates of the association of total dialkyl (Sigma DAP), diethyl (Sigma DEP), and dimethylphosphate (Sigma DMP) metabolite concentrations in maternal prenatal urine with mental and psychomotor development indices (MDI/PDI) and evaluated heterogeneity by children's center, race/ethnicity, and PON1 genotype. Results: There was significant heterogeneity in the center-specific estimates of association for Sigma DAP and Sigma DMP and the MDI (p = 0.09, and p = 0.05, respectively), as well as heterogeneity in the race/ethnicity-specific estimates for Sigma DAP (p = 0.06) and Sigma DMP (p = 0.02) and the MDI. Strong MDI associations in the CHAMACOS population per 10-fold increase in Sigma DAP (beta = -4.17; 95% CI: -7.00, -1.33) and Sigma DMP (beta = -3.64; 95% CI: -5.97, -1.32) were influential, as were associations among Hispanics (beta per 10-fold increase in Sigma DAP = -2.91; 95% CI: -4.71, -1.12). We generally found stronger negative associations of Sigma DAP and Sigma DEP with the 24-month MDI for carriers of the 192Q PON1 allele, particularly among blacks and Hispanics. Conclusions: Data pooling was complicated by center-related differences in subject characteristics, eligibility, and changes in regulations governing residential use of OPs during the study periods. Pooled summary estimates of prenatal exposure to OPs and neurodevelopment should be interpreted with caution because of significant heterogeneity in associations by center, race/ethnicity, and PON1 genotype. Subgroups with unique exposure profiles or susceptibilities may be at higher risk for adverse neurodevelopment following prenatal exposure.